Saturated fat intake modulates the association between an obesity genetic risk score and body mass index in two U.S. populations

Authors: CASAS-AGUSTENCH, PATRICIA - Tufts University; ARNETT, DONNA - University Of Alabama; SMITH, CAREN - Tufts University; LAI, CHAO-QIANG - Tufts University; PARNELL, LAURENCE - Tufts University; BORECKI, INGRID - Washington University School Of Medicine; FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); ALLISON, MATTHEW - University Of California; CHEN, YII-DER IDA - Harbor-Ucla Medical Center; TAYLOR, KENT - Harbor-Ucla Medical Center; RICH, STEPHEN - University Of Virginia School Of Medicine; ROTTER, JEROME - Harbor-Ucla Medical Center; ORDOVAS, JOSE - Tufts University

Submitted to: Journal of the Academy of Nutrition and Dietetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2014
Publication Date: 12/1/2014
Citation: Casas-Agustench, P., Arnett, D.K., Smith, C.E., Lai, C., Parnell, L.D., Borecki, I.B., Frazier-Wood, A.C., Allison, M., Chen, Y., Taylor, K.D., Rich, S.S., Rotter, J.I., Ordovas, J.M. 2014. Saturated fat intake modulates the association between an obesity genetic risk score and body mass index in two U.S. populations. Journal of the Academy of Nutrition and Dietetics. 114(12):1954-1966.

Interpretive Summary: We know that genes and diet both contribute to obesity risk. The objective of this study was to see whether genes interact with fat intake (an important component of overall diet) to influence body mass index (BMI). We found significant interactions between total fat intake and the obesity genes in two large, independent samples of male and female adults. These interactions were even stronger when assessing saturated fat interactions with genes on BMI. Because we analyzed the effect of fat on obesity risk, in the context of genetics, these findings have important implications for personalized dietary recommendations to prevent obesity in adults: if replicated we suggest that it is particular important for those whose genes predispose them to obesity to reduce fat in their diet.

Technical Abstract: Combining multiple genetic variants related to obesity into a genetic risk score (GRS) might improve identification of individuals at risk of developing obesity. Moreover, characterizing gene-diet interactions is a research challenge to establish dietary recommendations to individuals with higher predisposition to obesity. Our objective was to analyze the association between an obesity GRS and body mass index (BMI)in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)population, focusing on gene-diet interactions with total fat and saturated fatty acid (SFA) intake, and to replicate findings in the Multi-Ethnic Study of Atherosclerosis (MESA) population. Cross-sectional analyses included 783 white US participants from GOLDN and 2,035 from MESA. Dietary intakes were estimated with validated food frequency questionnaires. Height and weight were measured. A weighted GRS was calculated on the basis of 63 obesity-associated variants. Multiple linear regression models adjusted by potential confounders were used to examine gene-diet interactions between dietary intake (total fat and SFA) and the obesity GRS in determining BMI. Significant interactions were found between total fat intake and the obesity GRS using these variables as continuous for BMI (P for interaction=0.010, 0.046, and 0.002 in GOLDN, MESA, and meta-analysis, respectively). These association terms were stronger when assessing interactions between SFA intake and GRS for BMI (P for interaction=0.005,0.018,and <0.001 in GOLDN, MESA,and meta-analysis, respectively). SFA intake interacts with an obesity GRS in modulating BMI in two U.S. populations. Although determining the causal direction requires further investigation, these findings suggest that potential dietary recommendations to reduce BMI effectively in populations with high obesity GRS would be to reduce total fat intake mainly by limiting SFAs.